Ole Miss opens the post-Lane Kiffin era with its high-powered offense against a defense-first Louisville squad in a featured Week 1 college football matchup. Pete Golding remains in charge after steering the Rebels to the College Football Playoff semifinals once Kiffin left for LSU, and quarterback Trinidad Chambliss is back after receiving a sixth year of eligibility. Louisville has posted 9- or 10-win seasons in each of Jeff Brohm’s three years at the helm, and Lincoln Kienholz, the 2023 national high school player of the year, finally gets his first career start after two seasons as a backup at Ohio State. Visit our DraftKings promo code review and get $200 in bonus bets as a new user after $5+ in wagers here:

Kickoff for the neutral-site game is set for 7:30 p.m. ET at Nissan Stadium in Nashville. The Rebels are 6.5-point favorites in the latest Louisville vs. Ole Miss odds, while the over/under is 55.5. Before making any Louisville vs. Ole Miss picks, check out the college football predictions from expert Zack Cimini.

A Las Vegas handicapper, Cimini has returned a profit across multiple sports. Over the past three college football seasons, Cimini is 91-68-2, returning $1,420 to $100 bettors. He also enters the 2026 college football season on a 22-9 run (+1068) over his last 31 ATS picks. Anybody following his college football betting picks at sportsbooks and on betting sites could have seen huge returns.

Now, Cimini has analyzed Louisville vs. Ole Miss from every angle. You can visit SportsLine now to see his picks. Here are the FBS college football odds and trends for Ole Miss vs. Louisville:

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Top Louisville vs. Ole Miss predictions for Dublin

After analyzing Louisville vs. Ole Miss, Cimini is leaning Over (55.5 points) on the total. Ole Miss’s offense is the driver. Chambliss and RB Kewan Lacy are back from a group that ranked near the top of the country in yards and scored 36.1 ppg last year. Louisville’s red-zone efficiency was elite last season (90%), and Ole Miss wasn’t far behind.

Kienholz is an x-factor. He has the prep pedigree, but is making his first career start behind a rebuilt line that is already missing its starting left tackle. That points to a potentially run-heavy approach from Brohm. That said, the Cards averaged nearly 190 rush yards per game in the final three of 2025.

Cimini is expecting a higher-scoring contest and leaning towards the Over. See Cimini’s Louisville vs. Ole Miss spread pick at SportsLine.

How to make Louisville vs. Ole Miss picks

In addition to leaning Over on the total, Cimni has identified a critical x-factor which makes one side of the spread a must-back. You can only get the pick at SportsLine. 

So who wins Louisville vs. Ole Miss, and what crucial x-factor makes one side of the spread a must-back? Visit SportsLine now to see which side of the spread to jump on, all from the expert who’s on a 22-9 run (+1068) over his last 31 CFB spread picks, and find out.